Role of the DNAJ/HSP40 family in the pathogenesis of insulin resistance and type 2 diabetes

Ageing Res Rev. 2021 Mar 3:101313. doi: 10.1016/j.arr.2021.101313. Online ahead of print.ABSTRACTInsulin resistance (IR) underpins a wide range of metabolic disorders including type 2 diabetes (T2D), metabolic syndrome and cardiovascular diseases. IR is characterized by a marked reduction in the magnitude and/or delayed onset of insulin to stimulate glucose disposal. This condition is due to defects in one or several intracellular intermediates of the insulin signaling cascade, ranging from insulin receptor substrate (IRS) inactivation to reduced glucose phosphorylation and oxidation. Genetic predisposition, as well as other precipitating factors such as aging, obesity, and sedentary lifestyles are among the risk factors underlying the pathogenesis of IR and its subsequent progression to T2D. One of the cardinal hallmarks of T2D is the impairment of the heat shock response (HSR). Human and animal studies provided compelling evidence of reduced expression of several components of the HSR (i.e. Heat shock proteins or HSPs) in diabetic samples in a manner that correlates with the degree of IR. Interventions that induce the HSR, irrespective of the means to achieve it, proved their effectiveness in enhancing insulin sensitivity and improving glycemic index. However, most of these studies have been focused on HSP70 family. In this review, we will focus on the novel role of DNAJ/HSP40 cochaperone family in metabolic diseases associated with IR.PMID:33676026 | DOI:10.1016/j.arr.2021...
Source: Ageing Research Reviews - Category: Genetics & Stem Cells Authors: Source Type: research